It is the purpose of these experiments to examine the process of sensitization to cocaine following pretreatment with a number of pharmacological agents. It is our aim to evaluate the idea that at least part of the basis for variability in response to the rewarding effects of cocaine Is due to differences in the development of specific neurochemical systems, which in turn is due to environmental conditions. Rats will be exposed to four compounds (nicotine, caffeine, cocaine or amphetamine) for various periods of time. We will compare the ability for exposure to these compounds to alter the motor activating effects of cocaine and the propensity to self-administer this drug. Should the results show that preexposure to some agents can after the acquisition of cocaine self-administration, they will provide us with a realistic approach to prevention of abuse of this compound. We will also examine the neurochemical basis for changes in sensitivity produced by the preexposure regimen using microdialysis probes to measure the changes in extracellular dopamine within the nucleus accumbens and medial prefrontal cortex. Taken together, it is our hope that this line of investigation will demonstrate the importance of environmental factors as predisposing to drug abuse and will provide avenues leading to prevention of this compulsive self-destructive behavior.